Although many in vitro and in vivo studies have detected mutagenic effects from fluoride exposure, the Oral Health Research Institute at Indiana University’s School of Dentistry has repeatedly failed to find any such effect in multiple studies on the subject. According to its website, “The Oral Health Research Institute is a major site for contract testing of dental products required by the FDA and for product approval by the American Dental Association (ADA).” The following are four studies that the Institute has published on the subject of fluoride and mutagen:

“Two studies were conducted to assess the potential for adverse physiologic and genotoxic effects of long-term fluoride ingestion in adults residing in three communities with varying water fluoride levels (0.2 ppm, 1.0 ppm, and 4.0 ppm). All were long-time (> or = 30 years) residents of their respective communities. Plasma and urine samples were collected for fluoride analyses. Additional plasma was collected to determine blood chemistry, and plasma lymphocytes were examined to determine the frequency of sister chromatid exchange. Significant differences in urine (P = 0.001) and plasma (P = 0.0001) fluoride levels were found in the three communities. Seven of the blood parameters were statistically different among the communities, although all were within the defined normal range of the pathology laboratory. Sister chromatid exchange frequency was statistically higher in the 4.0 ppm fluoride community as compared to the other communities. Because of the higher SCE frequency in the 4.0 ppm fluoride community, a second study was performed to determine if the increased frequency was potentially related to the fluoride level of the communal water supply. Of the 58 adults recruited; 30 had used city water and 28 had used well water (< or = 0.3 ppm fluoride) as their principal water source for 30 years. Data analyses showed that the sister chromatid exchange frequency did not differ between the groups, indicating that the increased sister chromatid exchange frequency was not related to the fluoride level of the communal water. The investigation provided evidence that the long-term ingestion of water containing 4.0 ppm fluoride did not have any clinically important physiologic or genotoxic effects in healthy adults.
SOURCE: Jackson RD, et al. (1997). Lack of effect of long-term fluoride ingestion on blood chemistry and frequency of sister chromatid exchange in human lymphocytes. Environmental and Molecular Mutagenesis. 29:265-71.

The genetic toxicity of fluoride has been investigated extensively by various test systems. However, results obtained have been inconsistent. Fluoride has been reported to be non-genotoxic, genotoxic, and synergistic or antagonistic with certain mutagens. To date, there are no published human studies on the genotoxicity of fluoride. The purpose of this investigation was to determine genotoxic risks of long-term exposure to various concentrations of fluoride in drinking water in humans with normal or inadequate nutrition. Six groups of subjects with either normal or inadequate nutritional intakes were selected from areas of approximately 0.2, 1.0, or 4.8 ppm (10.5, 52.6, or 252.6 mumol/L) fluoride in water. The subjects had been continuous residents in the area for at least 35 years. Samples of drinking water, plasma, and urine were analyzed for fluoride content. Blood lymphocytes were examined to determine the frequency of sister chromatid exchange (SCE). Blood chemistry and electrolytes were also analyzed. The results showed that average daily fluoride intake as well as urine and plasma fluoride levels increased with increase in the fluoride content of the drinking water. The blood chemistry and electrolyte values were within the normal range for all populations, but several parameters were significantly different. While the numerical differences were small, the subjects with low fluoride in the water (0.11 and 0.23 ppm or 5.8 and 12.1 mumol/L) had significantly higher SCE frequencies than those with higher fluoride exposures.
SOURCE: Li Y, et al. (1995). Long-term exposure to fluoride in drinking water and sister chromatid exchange frequency in human blood lymphocytes. Journal of Dental Research 74:1468-74.

“This study was conducted to test the hypothesis that physiological changes which occur during aging increase the biological impact of fluoride and reduce the threshold of safe fluoride exposure. Four groups of rats were fed a low-fluoride diet (< 1.2 ppm) ad libitum and received 0, 5, 15, or 50 ppm fluoride in their drinking water. Animals were killed after three, six, 12, or 18 months of treatment. Blood and urine were monitored for biochemical markers of tissue function, and plasma, urine, feces, and representative tissues were analyzed for fluoride. In addition, bone marrow cells from animals killed after 18 months of treatment were examined for frequency of sister chromatid exchange (SCE), a marker of genetic damage. Study results indicated that, within treatment groups, fluoride intake, excretion, and retention did not change significantly between three and 18 months. Fluoride concentration in soft tissues did not change with treatment duration in the fluoride-treated animals. Mineralized tissue fluoride concentration and the total fluoride in the carcasses increased continually as the animals aged. In spite of significant, dose-related differences in tissue fluoride levels which occurred in all age groups in this study, there were no indications that increased fluoride in the tissues caused any adverse physiological or genotoxic effects. None of the monitored clinical “wellness” markers of tissue integrity and function was altered by fluoride in a clinically significant manner. Therefore, there was no evidence from this study that aging reduces the threshold of safe chronic fluoride exposure.”
SOURCE: Dunipace AJ, et al. (1995). Effect of aging on animal response to chronic fluoride exposure. Journal of Dental Research 74(1):358-68.

“To determine the potential adverse effects, if any, of long-term fluoride ingestion in humans, samples were collected from 25 adult females taking daily doses of fluoride (mean, 23 mg elemental F) for the treatment of osteoporosis and from 38 osteoporotic female controls. Patients in the fluoridegroup had been receiving therapy for approximately 18 months with a mean duration of 4.2 years and had serum fluoride values of at least 10 mumol/l. Laboratory analyses for fluoride were conducted on plasma, urine and drinking water samples collected from each panelist. Blood was also collected for blood chemistry analyses and plasma lymphocytes were examined for the frequency of sister chromatid exchange (SCE). Plasma and urine fluoride levels were significantly different between the two groups, while water fluoride was not. The SCE frequency, a measurement of potential genotoxicity, did not differ between the two groups. Of the blood chemistry parameters measured, albumin, alkaline phosphatase, sodium, chloride, the albumin/globulin (A/G) ratio, indirect bilirubin, lactate dehydrogenase (LDH), and gamma-glutamyl transferase (GGT) were found to be significantly different between the two groups (P < or = 0.05). However, none of the mean group values were outside stated normal ranges for any of these parameters. We conclude that the risk of developing adverse systemic effects from the ingestion of fluoride, at dosages and for a duration comparable with that of our panel, is minimal.”
SOURCE: Jackson R, et al. (1994). The effect of fluoride therapy on blood chemistry parameters in osteoporotic females. Bone Mineral 27(1):13-23.